The presentation of SARS-CoV-2 peptides by the common HLA-A∗02:01 molecule

oleh: Christopher Szeto, Demetra S.M. Chatzileontiadou, Andrea T. Nguyen, Hannah Sloane, Christian A. Lobos, Dhilshan Jayasinghe, Hanim Halim, Corey Smith, Alan Riboldi-Tunnicliffe, Emma J. Grant, Stephanie Gras

Format: Article
Diterbitkan: Elsevier 2021-02-01

Deskripsi

Summary: CD8+ T cells are crucial for anti-viral immunity; however, understanding T cell responses requires the identification of epitopes presented by human leukocyte antigens (HLA). To date, few SARS-CoV-2-specific CD8+ T cell epitopes have been described. Internal viral proteins are typically more conserved than surface proteins and are often the target of CD8+ T cells. Therefore, we have characterized eight peptides derived from the internal SARS-CoV-2 nucleocapsid protein predicted to bind HLA-A∗02:01, the most common HLA molecule in the global population. We determined not all peptides could form a complex with HLA-A∗02:01, and the six crystal structures determined revealed that some peptides adopted a mobile conformation. We therefore provide a molecular understanding of SARS-CoV-2 CD8+ T cell epitopes. Furthermore, we show that there is limited pre-existing CD8+ T cell response toward these epitopes in unexposed individuals. Together, these data show that SARS-CoV-2 nucleocapsid might not contain potent epitopes restricted to HLA-A∗02:01.